title: STAT3 promotes motor neuron differentiation by collaborating with motor neuron-specific LIM complex.
abstract: The motor neuron (MN)-hexamer complex consisting of LIM homeobox 3, Islet-1, and nuclear LIM interactor is a key determinant of motor neuron specification and differentiation. To gain insights into the transcriptional network in motor neuron development, we performed a genome-wide ChIP-sequencing analysis and found that the MN-hexamer directly regulates a wide array of motor neuron genes by binding to the HxRE (hexamer response element) shared among the target genes. Interestingly, STAT3-binding motif is highly enriched in the MN-hexamer-bound peaks in addition to the HxRE. We also found that a transcriptionally active form of STAT3 is expressed in embryonic motor neurons and that STAT3 associates with the MN-hexamer, enhancing the transcriptional activity of the MN-hexamer in an upstream signal-dependent manner. Correspondingly, STAT3 was needed for motor neuron differentiation in the developing spinal cord. Together, our studies uncover crucial gene regulatory mechanisms that couple MN-hexamer and STAT-activating extracellular signals to promote motor neuron differentiation in vertebrate spinal cord.
authors.affiliation: Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul 151-742, Korea. leeseung@snu.ac.kr
authors.forename: Seunghee
authors.initials: S
authors.lastname: Lee
authors.forename: Rongkun
authors.initials: R
authors.lastname: Shen
authors.forename: Hyong-Ho
authors.initials: HH
authors.lastname: Cho
authors.forename: Ryuk-Jun
authors.initials: RJ
authors.lastname: Kwon
authors.forename: So Yeon
authors.initials: SY
authors.lastname: Seo
authors.forename: Jae W
authors.initials: JW
authors.lastname: Lee
authors.forename: Soo-Kyung
authors.initials: SK
authors.lastname: Lee
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D004742:Enhancer Elements, Genetic; D016678:Genome; D060850:LIM-Homeodomain Proteins / Q000378:metabolism*; D051379:Mice; D009046:Motor Neurons / Q000166:cytology*; D011485:Protein Binding; D050796:STAT3 Transcription Factor / Q000378:metabolism / Q000502:physiology*
chemical_list: D060850:LIM-Homeodomain Proteins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse
keywords: Isl1; LIF; LIM homeodomain factor; Lhx3; NLI